Discovery of Novel Piperidinylthiazole Derivatives As Broad-Spectrum Fungicidal Candidates

Oxathiapiprolin is one of the best
active fungicides discovered
for oomycetes control. To develop a fungicide candidate with a broad
spectrum of activity, 22 new piperidinylthiazole derivatives were
designed and synthesized. Compound 5l showed the best
activity against Pseudoperonospora cubensis (Berk.
et Curt.) Rostov and Phytophthora infestans in vivo
with 100% and 80% of inhibition, respectively, at 1 mg/L, and 72.87%
of field efficacy against P. cubensis at 1 g ai/667
m2 validated these results. Compound 5i exhibited
a broad spectrum of excellent activity against Sclerotinia
sclerotiorum with EC50 = 0.30 mg/L (>10 times
more active than oxathiapiprolin and azoxystrobin in vitro), good
activity against Botrytis cinerea, Cercospora
arachidicola, and Gibberella zeae with EC50 of 14.54, 5.57, and 14.03 mg/L in vitro and against P. cubensis and P. infestans with 60% and
30% inhibition rates, respectively, at 1 mg/L in vivo. Mode of action
studies by RNA sequencing analysis discovered oxysterol-binding protein
(OSBP), chitin synthase (CHS1), and (1,3)-β-glucan synthase
(FKS2) as the potent target of 5i against S.
sclerotiorum. Quenching studies validated that OSBP was the
same target of both 5i and oxathiapiprolin; it was quenched
by both of them. Our studies discovered isothiazole-containing piperidinylthiazole
as an OSBP target-based novel lead for fungicide development.